Breast cancer cell lines carry cell line-specific genomic alterations that are distinct from aberrations in breast cancer tissues: comparison of the CGH profiles between cancer cell lines and primary cancer tissues.
Breast cancer cell lines carry cell line-specific genomic alterations that are distinct from aberrations in breast cancer tissues: comparison of the CGH profiles between cancer cell lines and primary cancer tissues.
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DOI：
10.1186/1471-2407-10-15
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发表时间：
2010-01-14
期刊：
影响因子：
3.8
通讯作者：
Sasaki K
中科院分区：
文献类型：
--
作者：
Tsuji K;Kawauchi S;Saito S;Furuya T;Ikemoto K;Nakao M;Yamamoto S;Oka M;Hirano T;Sasaki K
细胞系常用于世界各地的各种生物医学研究。然而，目前仍不确定原发性肿瘤组织中存在的基因组改变是否在细胞系中有所体现，以及细胞系是否携带细胞系特异性基因组改变。本研究就是为了回答这些问题而进行的。采用基于阵列的比较基因组杂交 (CGH) 和 4030 个细菌人工染色体 (BAC)（以 1.0 兆碱基分辨率覆盖基因组）来分析 35 个原发性乳腺肿瘤和 24 个乳腺癌细胞系中的 DNA 拷贝数畸变 (DCNA)。比较这两组之间的 DCNA。将组织显微切割技术应用于原发性肿瘤组织，以减少正常组织成分对样品的污染。对于细胞系和原发性肿瘤组织，带有 DCNA 的 BAC 克隆的平均数量分别为 1832 个（斑点克隆的 45.3%）和 971 个（24.9%）。在 > 50% 的原发癌组织中检测到 1q 和 8q 的增加以及 8p、11q、16q 和 17p 的损失。这些畸变也经常在细胞系中检测到。除了这些改变之外，细胞系还表现出反复出现的基因组改变，包括 5p14-15、20q11 和 20q13 的增加以及 4p13-p16、18q12、18q21、Xq21.1 和 Xq26-q28 的损失，而这些改变在肿瘤组织标本中几乎未检测到。这些被认为是细胞系特异性 DCNA。 HER2扩增频率在细胞系和肿瘤组织中均较高，但在细胞系和原发肿瘤之间存在统计学差异（P = 0.012）；细胞系为 41.3 ± 29.9%，组织样本为 15.9 ± 18.6%。已建立的细胞系携带细胞系特异性 DCNA 以及在原发性肿瘤组织中检测到的反复畸变。因此必须强调的是，细胞系并不总是代表亲代肿瘤组织的基因型。
Cell lines are commonly used in various kinds of biomedical research in the world. However, it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. This study was performed to answer these questions. Array-based comparative genomic hybridization (CGH) was employed with 4030 bacterial artificial chromosomes (BACs) that cover the genome at 1.0 megabase resolution to analyze DNA copy number aberrations (DCNAs) in 35 primary breast tumors and 24 breast cancer cell lines. DCNAs were compared between these two groups. A tissue microdissection technique was applied to primary tumor tissues to reduce the contamination of samples by normal tissue components. The average number of BAC clones with DCNAs was 1832 (45.3% of spotted clones) and 971 (24.9%) for cell lines and primary tumor tissues, respectively. Gains of 1q and 8q and losses of 8p, 11q, 16q and 17p were detected in >50% of primary cancer tissues. These aberrations were also frequently detected in cell lines. In addition to these alterations, the cell lines showed recurrent genomic alterations including gains of 5p14-15, 20q11 and 20q13 and losses of 4p13-p16, 18q12, 18q21, Xq21.1 and Xq26-q28 that were barely detected in tumor tissue specimens. These are considered to be cell line-specific DCNAs. The frequency of the HER2 amplification was high in both cell lines and tumor tissues, but it was statistically different between cell lines and primary tumors (P = 0.012); 41.3 ± 29.9% for the cell lines and 15.9 ± 18.6% for the tissue specimens. Established cell lines carry cell lines-specific DCNAs together with recurrent aberrations detected in primary tumor tissues. It must therefore be emphasized that cell lines do not always represent the genotypes of parental tumor tissues.